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Mendeley readers
Attention Score in Context
| Title |
Phosphorylation of ΔNp63α via a Novel TGFβ/ALK5 Signaling Mechanism Mediates the Anti-Clonogenic Effects of TGFβ
|
|---|---|
| Published in |
PLOS ONE, November 2012
|
| DOI | 10.1371/journal.pone.0050066 |
| Pubmed ID | |
| Authors |
Pratima Cherukuri, Andrew J. DeCastro, Amanda L. Balboni, Sondra L. Downey, Jennifer Y. Liu, Justine A. Hutchinson, James DiRenzo |
| Abstract |
Genetic analysis of TP63 implicates ΔNp63 isoforms in preservation of replicative capacity and cellular lifespan within adult stem cells. ΔNp63α is also an oncogene and survival factor that mediates therapeutic resistance in squamous carcinomas. These diverse activities are the result of genetic and functional interactions between TP63 and an array of morphogenic and morphostatic signals that govern tissue and tumor stasis, mitotic polarity, and cell fate; however the cellular signals that account for specific functions of TP63 are incompletely understood. To address this we sought to identify signaling pathways that regulate expression, stability or activity of ΔNp63α. An siRNA-based screen of the human kinome identified the Type 1 TGFβ receptor, ALK5, as the kinase required for phosphorylation of ΔNp63α at Serine 66/68 (S66/68). This activity is TGFβ-dependent and sensitive to either ALK5-directed siRNA or the ALK5 kinase inhibitor A83-01. Mechanistic studies support a model in which ALK5 is proteolytically cleaved at the internal juxtamembrane region resulting in the translocation of the C-terminal ALK5-intracellular kinase domain (ALK5(IKD)). In this study, we demonstrate that ALK5-mediated phosphorylation of ΔNp63α is required for the anti-clonogenic effects of TGFΒ and ectopic expression of ALK5(IKD) mimics these effects. Finally, we present evidence that ultraviolet irradiation-mediated phosphorylation of ΔNp63α is sensitive to ALK5 inhibitors. These findings identify a non-canonical TGFβ-signaling pathway that mediates the anti-clonogenic effects of TGFβ and the effects of cellular stress via ΔNp63α phosphorylation. |
Mendeley readers
The data shown below were compiled from readership statistics for 22 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Austria | 1 | 5% |
| Unknown | 21 | 95% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 6 | 27% |
| Student > Ph. D. Student | 6 | 27% |
| Professor | 2 | 9% |
| Student > Master | 2 | 9% |
| Student > Bachelor | 1 | 5% |
| Other | 2 | 9% |
| Unknown | 3 | 14% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 8 | 36% |
| Biochemistry, Genetics and Molecular Biology | 3 | 14% |
| Medicine and Dentistry | 3 | 14% |
| Nursing and Health Professions | 2 | 9% |
| Neuroscience | 1 | 5% |
| Other | 1 | 5% |
| Unknown | 4 | 18% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 17 November 2012.
All research outputs
#20,172,971
of 22,685,926 outputs
Outputs from PLOS ONE
#172,801
of 193,650 outputs
Outputs of similar age
#141,200
of 159,110 outputs
Outputs of similar age from PLOS ONE
#3,987
of 4,755 outputs
Altmetric has tracked 22,685,926 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 193,650 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.0. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 159,110 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 4,755 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.